J Orthop Res. 2015 Nov;33(11):1580-6.
Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.
Yong-Beom Park, Minjung Song, Choong-Hee Lee, Jin-A Kim, Chul-Won Ha
Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.
hUCB-MSCs and hyaluronic acid hydrogel composite – a novel therapeutic option for cartilage repair
Articular cartilage has very limited capacity for repair because of its avascular nature and its specialized structure and composition. Currently available methods for the repair of articular cartilage have disadvantages of size limitation, limited donor cell availability and donor site morbidity. In addition, the quality of the repair tissue is still far from ideal because of high percentage of fibrocartilage in the repair tissue. Therefore, the predictability and durability of cartilage repair remains an unmet clinical need.
With the great therapeutic potential of MSCs, stem cell therapy has been regarded as the future solution to overcome various diseases. In particular, umbilical cord blood(UCB) has emerged as an alternative cellular source to obtain MSCs because they are easy to acquire and store, and they can afford a large scale in MSC numbers as “very young” status.
In the articular cartilage repair with cells, hydrogels have been utilized as an optimal delivery vehicle, because they possess several advantages, such as high cell seeding efficacies and the abilities to transport nutrients, ability to fill defects of any size and suspend cells homogenously, and injectability as a liquid that gels at body temperature and rebuild the three-dimensional structure (Hofman AS, 2002). However, proper hydrogels for delivering hUCB-MSCs have not been well investigated.
Figure 1. Articular cartilage defects in a rat model. The patella was laterally dislocated and full-thickness articular cartilage defects (2mm diameter) were created through subchondral bone in the trochlear groove in each hindlimb. And after removing cartilage and bone debris, composites of hUCB-MSCs and different hydrogels were transplanted into defects.
In this study, we have transplanted the composites of human UCB-MSCs and different hydrogels (hyaluronic acid, hyaluronic acid: pluronic (1:1) and hyaluronic acid: pluronic:chitosan (1:1:2)) in critical-sized full-thickness cartilage defect and evaluated the human UCB-MSCs as a novel cell sources in cartilage repair and determined the most suitable delivering hydrogel (Figure 1). The hUCB-MSCs were isolated and cultured as previously published (Yang and Ha, 2004). The repair tissues by the hUCB-MSCs transplantation resembled articular cartilage, integrated well to the adjacent cartilage and restored smooth articular surface without fissures or cracks. In histological evaluation, hUCB-MSCs with different hydrogels showed overall superior cartilage repair compared to hydrogel only. In quantitative analysis, among the three hydrogels investigated in this study, hUCB-MSCs with 4% hyaluronic acid hydrogel composite showed significant high score compared to hUCB-MSCs with 4% hyaluronic acid/30% pluronic (1:1, v/v) or 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v).
The results of the present study showthat 4% hyaluronic acid is a suitable delivering hydrogel for cartilage repair. The hUCB-MSCs with hydrogels showed cartilage repair potential in a rat model. These findings suggest that hUCB-MSCs are a promising cell source and the composite of hUCB-MSCs and 4 % hyaluronic acid is a feasible and effective therapeutic option for articular cartilage repair.
Figure 2. Masson’s trichrome staining (A) and Sirius red staining (B) at 8 weeks post-transplantation.
Yang SE, Ha CW, Jung M, et al. 2004. Mesenchymal stem/progenitor cells developed in cultures from UC blood. Cytotherapy 6:476-486.
Hoffman AS. 2002. Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3-12.
Acknowledgements: This study was supported by the Korean Ministry of Health and Welfare (HI12C1826) and the National Research Foundation of Korea (2013R1A1A1075992).The funding sources had no involvement in the study design, collection, analysis or interpretation of the data, writing of the manuscript, or in the decision to submit the manuscript for publication.
Chul-Won Ha, M.D., Ph.D.
Director of Stem Cell and Regenerative Medicine Institute
Chief of Knee Service (Arthroplasty, Arthroscopy and Sports Medicine)
Department of Orthopedic Surgery Samsung Medical Center
Sungkyunkwan University School of Medicine
81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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